Gabapentin hybrid peptides and bioconjugates

Abstract Synthetic approaches to gabapentin bioconjugates that overcome the tendency of gabapentin to cyclize into its γ-lactam are studied. Gabapentin was converted by N-acylation at its N-terminus into di-, tri-, and tetrapeptides ( l -Ala-Gbp, l -Val-Gbp, l -Ala- l -Phe-Gbp, Gly- l -Ala-β-Ala-Gbp). Carboxyl-activated Boc-protected gabapentin was used to N -, O -, and S -acylate small peptides and hormones to give conjugates that could also provide prodrugs containing conformationally constrained gabapentin units.